A randomized, double-blinded, placebo controlled crossover study was conducted in 16 patients with painful diabetic peripheral neuropathy to assess the short-term efficacy and tolerability of inhaled cannabis. In a cross-over design, each participant was exposed to a single dosing session of placebo, low (1% tetrahydrocannabinol, THC), medium (4% THC), or high (7% THC) doses of cannabis. Baseline spontaneous pain, evoked pain and cognitive testing were performed. Subjects were then administered aerosolized cannabis or placebo and the pain intensity and subjective highness score was measured at 5, 15, 30, 45, and 60 minutes and then every 30 minutes for an additional 3 hours. Cognitive testing was performed at 5 and 30 minutes and then every 30 minutes for an additional 3 hours. The primary analysis compared differences in spontaneous pain over time between doses using linear mixed effects models. There was a significant difference in spontaneous pain scores between doses (p<0.001). Specific significant comparisons were placebo versus low, medium, high dose (p = 0.031, 0.04 and <0.001 respectively) and high versus low, medium (both p<0.001). There was a significant effect of the high dose on foam brush and von Frey evoked pain (both p<0.001). There was a significant negative effect (impaired performance) of the high dose on two of the three neuropsychological tests (Paced Auditory Serial Addition Test, Trail Making Test B.

Objectives Hispanics are the fastest growing ethnicity in the United States, yet there are limited well-validated neuropsychological tools in Spanish, and an even greater paucity of normative standards representing this population. The Spanish NIH Toolbox Cognition Battery (NIHTB-CB) is a novel neurocognitive screener; however, the original norms were developed combining Spanish- and English-versions of the battery. We developed normative standards for the Spanish NIHTB-CB, fully adjusting for demographic variables and based entirely on a Spanish-speaking sample. Methods A total of 408 Spanish-speaking neurologically healthy adults (ages 18–85 years) and 496 children (ages 3–7 years) completed the NIH Toolbox norming project. We developed three types of scores: uncorrected based on the entire Spanish-speaking cohort, age-corrected, and fully demographically corrected (age, education, sex) scores for each of the seven NIHTB-CB tests and three composites (Fluid, Crystallized, Total Composites). Corrected scores were developed using polynomial regression models. Demographic factors demonstrated medium-to-large effects on uncorrected NIHTB-CB scores in a pattern that differed from that observed on the English NIHTB-CB. For example, in Spanish-speaking adults, education was more strongly associated with Fluid scores, but showed the strongest association with Crystallized scores among English-speaking adults. Results Demographic factors were no longer associated with fully corrected scores. The original norms were not successful in eliminating demographic effects, overestimating children’s performances, and underestimating adults’ performances on the Spanish NIHTB-CB. Conclusions The disparate pattern of demographic associations on the Spanish versus English NIHTB-CB supports the need for distinct normative standards developed separately for each population. Fully adjusted scores presented here will aid in more accurately characterizing acquired brain dysfunction among U.S. Spanish-speakers.

Higher levels of physical activity (PA) have been linked to better neurocognitive functioning in many populations. The current study examines the longitudinal association between PA and neurocognitive functioning among HIV-infected and HIV-uninfected persons. Community-dwelling adults (N = 291) self-reported level of PA and completed a comprehensive neuropsychological battery at two to four study visits (Mean follow-up time = 2.6 years). Participants were divided into three PA groups: ''No PA'' (no PA at any visit), ''consistent PA'' (PA at C50% of visits), and ''inconsistent PA'' (PA \ 50% of visits). A mixed effect model, adjusting for significant covariates showed that all PA groups had statistically significant, yet modest, neurocognitive decline over time; and, the consistent PA group began with, and maintained, significantly better neurocognitive function compared to the other two PA groups. This effect was evident among both HIV-uninfected and HIV-infected persons, despite the fact that HIV-infected persons showed lower baseline neurocognitive function. PA is a modifiable lifestyle behavior that may help to protect against neurocognitive impairment regardless of HIV status, however, given the proportion of HIV-infected individuals who evidence neurocognitive difficulties, a focus on increasing PA seems warranted.Resumen La actividad física (AF) ha sido asociada con un mejor funcionamiento neurocognitivo en varios grupos. Este estudio examinó la asociación longitudinal entre la AF y el funcionamiento neurocognitivo en personas con y sin infección del VIH. Adultos viviendo en la comunidad (N = 291) proporcionaron información acerca de sus niveles de AF y completaron una batería neuropsicológica exhaustiva. Los participantes completaron entre dos y cuatro visitas relacionadas con el estudio (tiempo de seguimiento promedio = 2,6 años) y fueron divididos en tres grupos de AF: ''Ninguna AF'' (Ninguna AF durante todas las visitas del estudio), ''AF Consistente'' (AF durante 50% o más de las visitas del estudio), y ''AF Inconsistente'' (AF durante menos del 50% de las visitas del estudio). Un modelo estadístico mixto, ajustando por el efecto de variables externas, indicó que hubo una reducción estadísticamente significativa, pero poco pronunciada, en el funcionamiento neurocognitivo en todos los grupos. Además, el grupo con AF Consistente demostró un mejor funcionamiento neurocognitivo en comparación con los otros dos grupos de AF al comienzo del estudio, el cual se mantuvo durante el seguimiento. A pesar de que las personas con VIH demostraron un funcionamiento neurocognitivo más bajo al comienzo del estudio que las personas sin VIH, el efecto de AF fue demostrado en los dos grupos. Es importante recalcar que la AF es un factor de vida modificable que podría proteger contra los daños neurocognitivos independientemente de si las personas tienen o no VIH. Dada la proporción de personas con VIH que demuestran problemas neurocognitivos relacionados con esta enfermedad, será importante enfocar los esfuerzos ...

Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes.